Isoform‐selective glucuronidation of triclosan

Abstract

The antibacterial substance triclosan, 5‐chloro‐2‐(2,4‐dichlorophenoxy)‐phenol, is used in many consumer products resulting in widespread human exposure. Triclosan forms glucuronide and sulfate conjugates which are excreted in urine, however it is not known which UDP‐glucuronosyltransferase (UGT) isoform(s) catalyze triclosan glucuronidation. This study examined rates of glucuronidation of several concentrations of triclosan catalyzed by expressed human UGTs and individual human liver microsomes (HLMs) with 1 mM 14C‐UDP‐glucuronic acid as co‐substrate. The UGT isozymes studied are found in the human liver and intestine, the likely sites of triclosan glucuronidation. The results indicated UGT1A1 exhibited the highest glucuronidation efficiency (Vmax/Km). UGTs 1A3, 1A6,1A7, 1A8 and 1A9 also readily catalyzed triclosan glucuronidation, but UGTs 1A4, 1A10, 2B4, 2B7 and 2B15 were less active. Studies of triclosan glucuronidation in 23 individual HLMs were conducted at 0.01 mM and 1mM triclosan concentrations. More than 15‐fold variability in specific activity was found in the HLM samples at both concentrations of triclosan. These results suggest that clearance of triclosan by glucuronidation may be expected to vary considerably between individuals. Supported in part by R21 ES 020545 and an award from the University of Florida